Biology subjects

Itoh, H.

Publications and source records attributed to Itoh, H..

14 recordsLinked to original sources

bioRxiv2026

SAR11 Genome Atlas: a genome and gene catalog for functional profiling of the most abundant bacterial clade in the ocean

The SAR11 clade, also known as the order Candidatus Pelagibacterales, is among the most abundant bacterial lineages in the ocean and plays central roles in marine biogeochemical cycles. However, many SAR11 genes remain functionally uncharacterized, highlighting the need for a comprehensive, integrated catalog that supports genomic, functional, and ecological analyses across the clade. Here, we present the SAR11 Genome Atlas, an interactive ortholog group (OG)-centered web resource that integrates 542 SAR11 genomes, including all 132 cultured strain genomes, with functional annotations, synteny, phylogenetic distribution, metatranscriptomic expression, and predicted protein structure information. To demonstrate its utility, we used environmental expression profiles to identify OGs associated with high-latitude environments, recovering OGs known to be involved in cold adaptation and proposing a hypothesis for the function of uncharacterized protein. We further analyzed phylogenetic distribution patterns to identify mutually exclusive functional modules, including candidate alternative systems for Mn/Zn homeostasis and phosphate acquisition, and to associate these modules with distinct oceanographic environments. Together, these case studies demonstrate that the SAR11 Genome Atlas supports complementary analyses that connect environmental signals to genes of interest and use phylogenetic or functional distributions to generate hypotheses about ecological specialization. Through a user-friendly web interface, the SAR11 Genome Atlas enables researchers to explore genomic, environmental, and structural information without specialized computational expertise. All data and analysis outputs are freely accessible online at [https://stsnsn.github.io/SAR11_Atlas/]. The SAR11 Genome Atlas thus provides a scalable framework for generating and testing hypotheses that connect SAR11 genomic variation to protein function and oceanographic context, supporting advances in marine microbial ecology and biogeochemistry.

microbiology↗

bioRxiv2026

Genomic, spatial, and evolutionary insights into a dominant Mycoplasmatota symbiont colonizing the body wall of deep-sea holothurians

Subcuticular bacteria (SCB) are widespread symbionts of echinoderms and often dominate the body-wall microbiome, suggesting important roles in host physiology. However, their diversity, metabolic properties, and host associations remain poorly characterized. Here, we report a novel dominant SCB lineage associated with deep-sea holothurians, Scotoplanes spp. collected from the Northwest Pacific. We recovered two high-quality genomes, including a 649-kb complete circular genome, and propose a new genus and species, "Candidatus Abyssoplasma scotoplanesicola", within Mycoplasmatota. The two genomes showed a highly reduced metabolic repertoire, lacking central pathways including glycolysis. In contrast, acidic cell-surface-associated proteins, including large proteins exceeding 5,000 amino acids, accounted for 27.6% of the complete genome and clustered near defense islands. Localized genome plasticity in these regions, revealed by comparison between the two closely related genomes, suggests a possible mechanism for diversification of cell-surface proteins at the host-symbiont interface. "Candidatus Abyssoplasma scotoplanesicola" occupied 76.4-98.9% of the body-wall microbiome of the Scotoplanes specimens. Fluorescence in situ hybridization analysis confirmed that these bacteria formed aggregates on the epidermal side of the body wall. Overall, this study provides genome-and spatially resolved views of dominant SCB in holothurians and offers evolutionary insights into host-interface diversification in the deep-sea holothurian body wall.

microbiology↗

bioRxiv2025

Soil pH as an external filter shaping insect-microbe gut symbiosis

BackgroundMany animals and plants establish intimate symbiotic relationships with specific microorganisms acquired from the environment. Given the immense diversity of environmental microbiomes, selecting appropriate partners from such a vast microbial pool poses a critical challenge for host organisms. To meet this challenge, hosts have evolved sophisticated internal partner-choice mechanisms that ensure stable associations with beneficial microbes. However, because these symbionts primarily inhabit external environments, environmental conditions themselves are also expected to play pivotal roles in the establishment of symbiosis. Despite this expectation, the mechanistic role of external environmental filters in shaping the intended symbiosis remains largely unexplored. Focusing on stink bugs, which acquire their symbiotic bacteria from soil each generation, we investigated how soil properties influence the establishment of gut symbiosis in terrestrial insects. ResultsMicrobiome analyses confirmed that Burkholderia sensu lato overwhelmingly dominates a specific gut organ in six stink bug species from the superfamilies Coreoidea and Lygaeoidea, including serious agricultural pests (relative abundance ranging from 74.5% to 100%). Rearing experiments with isolated Burkholderia revealed that insects were strictly dependent on this symbiont; failure to acquire it from soil severely reduced host growth and reproduction, indicating that the availability of symbionts from soil represents an ecological bottleneck. Field surveys identified patches of exceptionally high stink bug density in weedy fields with soil pH <7.0, whereas such aggregations were absent in fields with pH [≥]7.0. Laboratory experiments with collected field soils showed that the abundance of Burkholderia in soils was negatively correlated with soil pH, and stink bugs readily acquired their symbionts from soils with pH <7.0 but rarely from soils with pH [≥]7.0. Experimental manipulations of soil pH followed by rearing experiments confirmed that increasing soil pH to 7-8 markedly suppressed symbiont acquisition by the host, likely by impairing symbiont growth and motility. ConclusionsWe demonstrate that, beyond host-intrinsic mechanisms, a soil chemical property externally filters symbiotic bacteria prior to colonization inside the host. These findings reveal that, alongside host physiology, environmental conditions--mediated through the soil and host gut microbiomes--shape the assembly, maintenance, and evolution of host-microbe symbiotic associations.

microbiology↗

bioRxiv2025

Betaproteobacterial clade II nosZ activated under high N2O concentrations in paddy soil microcosms

AimsMicrobial communities in paddy soils act as potential sinks of nitrous oxide (N2O), a notorious greenhouse gas, but their potential to reduce external N2O is unclear. The direct observation of N2O reduction in submerged field soils is technically difficult. Here, we aimed to identify soil microbial clades that underpin the strong N2O mitigation capacity. Methods and ResultsWe constructed paddy soil microcosms with external N2O amendment that enabled the simultaneous evaluation of N2O reductase gene (nosZ) transcripts and N2O consumption. Although the amount of N2O amended was large, it was mostly consumed after 6- 8 days of microcosm incubation. Metatranscriptomic sequencing revealed that betaproteobacterial nosZ, especially those classified as clade II nosZ belonging to the orders Rhodocyclales or Nitrosomonadales, occupied >50% of the nosZ transcripts in three of the five paddy soils used. On the other hand, publicly available shotgun metagenomic sequences of 46 paddy soils were not dominated by betaproteobacterial clade II nosZ sequences, although they were ubiquitous. The same applied to the 16S rRNA sequences of Rhodocyclales or Nitrosomonadales. ConclusionsThe results indicated that betaproteobacterial N2O reducers potentially serve as powerful N2O sinks. Betaproteobacteria holding clade II nosZ can be targets of biostimulation, although further studies are required to understand their ecophysiology. Impact StatementOur results indicate that Rhodocyclales or Nitrosomonadales have the potential to serve as powerful N2O sinks in soils.

microbiology↗

bioRxiv2024

Wild gut microbiome suppresses the opportunistic pathogen Aeromonas in medaka under domesticated rearing conditions

BackgroundThe gut microbiome plays a crucial role in the metabolic health and pathogen resistance of various host animals. It is also well established that external environmental factors can influence the gut microbiome, leading to differences in its composition. However, the functional implications of these differences remain poorly understood. This study examined the gut microbiome of medaka (Oryzias latipes species complex) by comparing domesticated and wild populations, with the aim of gaining insights into the functional significance of their specific characteristics, particularly those of the wild-type microbiome. ResultsFor the comparative analysis of the gut microbiome, 48 domesticated and 122 wild medaka were collected from multiple laboratories, pet stores and streams across Japan. The results showed that wild medaka exhibited significantly higher gut microbiome diversity, with a broader range of bacterial members. In contrast, the gut microbiome of domesticated medaka harbored lower microbial diversity and was consistently dominated by Aeromonas, a typical opportunistic pathogen in fish. Additionally, 88.6% of Aeromonas isolates from domesticated medaka exhibited haemolytic activity. Moreover, a domesticated rearing experiment with wild populations showed no proliferation or dominance of Aeromonas in their gut, as observed in domesticated medaka. A further rearing experiment revealed that pre-exposing antibiotic-treated medaka to sediments from their natural habitats prevented Aeromonas colonisation, even when reared under domesticated conditions. ConclusionsThese findings suggest that the habitat-derived wild gut microbiome can inhibit Aeromonas proliferation in domesticated fish, highlighting its potential to mitigate opportunistic diseases in aquaculture.

microbiology↗

bioRxiv2024

Phosphodiesterase 3 inhibitors boost bone outgrowth

C-type natriuretic peptide (CNP) stimulates skeletal growth by acting on the growth plates of long bones, and a CNP variant is clinically used for achondroplasia treatment. We previously reported that CNP stimulates the autonomic Ca2+ influx mediated by TRPM7 channels in growth plate chondrocytes to facilitate extracellular matrix synthesis for bone growth. Here, we report that phosphodiesterase 3 (PDE3) inhibitors facilitate the Ca2+ influx and promote bone outgrowth. The representative PDE3 inhibitor cilostazol elevated cGMP levels and activated cell-surface K+ channels probably due to protein kinase G-mediated phosphorylation in growth-plate chondrocytes. The resulting hyperpolarization likely facilitated TRPM7-mediated Ca2+ influx by increasing the Ca2+-driving force. Moreover, cilostazol simulated the elongation of cultured bones and enlarged the body size of juvenile mice. Several PDE3 inhibitors have been used for clinical treatment of thrombosis, heart failure and asthma, while our observations suggest that the repositioning of PDE3 inhibitors would provide novel medications for syndromes involving short stature.

pharmacology and toxicology↗

bioRxiv2023

Astrocyte-specific inhibition of primary cilium functions improves cognitive impairment during neuroinflammation by suppressing A1 astrocyte differentiation.

A1 astrocytes play a neurotoxic role in various neurodegenerative diseases. While inhibiting the differentiation of A1 astrocytes can slow disease progression, the mechanisms controlling A1 astrocyte differentiation are largely unknown. The primary cilium is a cellular organelle that receives extracellular signals and regulates cell proliferation, differentiation, and maturation. To elucidate the physiological function of the primary cilium in A1 astrocytes, we utilized primary astrocytes and an inflammation mouse model. We found that the length of the primary cilium was increased in astrocytes, and the inhibition of primary cilium formation inhibited their differentiation into A1 astrocytes. Since mice with systemic ciliogenesis defects exhibit embryonic lethality, the function of the primary cilium in adults has remained largely unclear. Therefore, we established conditional knockout (cKO) mice that specifically inhibit primary cilium function in astrocytes upon drug stimulation. In a neuroinflammation mouse model in which lipopolysaccharide (LPS) was intraperitoneally injected into wild-type mice, increases in A1 astrocyte number and primary cilium length were observed in the brain. In contrast, cKO mice exhibited a reduction in the proportions of A1 astrocytes and apoptotic cells in the brain. Additionally, the novel object recognition (NOR) score observed in the cKO mice was higher than that observed in the neuroinflammation model mice. These results suggest that the primary cilium in astrocytes is essential for A1 astrocyte differentiation, which leads to a decline brain function. We propose that regulating astrocyte-specific primary cilium signalling may be a novel strategy for the suppression of neuroinflammation.

neuroscience↗

bioRxiv2023

qMaLioffG: A single green fluorescent protein FLIM indicator enabling quantitative imaging of endogenous ATP

The widespread use of fluorescence lifetime imaging microscopy (FLIM) for quantitative imaging is hindered by the limited availability of a FLIM-based genetically encoded indicator using a conventional 488 nm laser. Here, we present qMaLioffG, a single green fluorescent protein FLIM indicator showing a fluorescence lifetime change in ATP concentration within the physiological range. This allows quantitative imaging of endogenous ATP to investigate cellular energy status of different cell types.

biophysics↗

bioRxiv2023

Neutralizing antibody levels and epidemiological information of patients with breakthrough COVID-19 infection in Toyama, Japan

Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many cases without neutralizing activity or BI were immunosuppressed individuals. The results of this study show that BI occurs even when there are sufficient neutralizing antibodies in the blood due to exposure to close contacts at the time of infection. Thus, even after vaccination, sufficient precautions must be taken to prevent infection.

microbiology↗

bioRxiv2023

Deciphering transcriptomic signatures explaining the phenotypic plasticity of non-heading lettuce genotypes under artificial light conditions

Elucidating the mechanisms and pathways involved in genotype-environment (GxE) interactions and phenotypic plasticity is critical for improving plant growth. Controlled environment agricultural systems allow growers to modulate the environment for particular genotypes. In this study, we evaluated the effects of interactions among 14 genotypes and four artificial light environments on leaf lettuce phenotypes and dissected the underlying molecular mechanism via transcriptome-based modeling. Variations in morphological traits and phytochemical contents in response to artificial light treatments revealed significant GxE interactions. The appropriate genotype and artificial light combinations for maximizing phenotypic expression were determined on the basis of a joint regression analysis and the additive main effect and multiplicative interaction model for these GxE interactions. Transcriptome-based regression modeling explained approximately 50%-90% of the GxE variations. Further analyzes indicated Red Lettuce Leaves 4 (RLL4) regulates UV-B and blue light signaling through the effects of the HY5-MBW pathway on flavonoid biosynthesis and contributes to natural variations in the light-responsive plasticity of lettuce traits. Our study represents an important step toward elucidating the phenotypic variations due to GxE interactions in non-heading lettuce under artificial light conditions. HighlightsO_LISeveral morphological characteristics of lettuce genotypes were altered by different light wavelengths. C_LIO_LIA defective RLL4 allele (rll4) induces the expression of downstream genes related to UV-B and blue light signaling through activation of the HY5-MBW pathway, which enhances phytochemical accumulation in lettuce. C_LIO_LIGxE analyzes identified the ideal genotype and artificial light combinations for individual phenotypes. C_LIO_LITranscriptome-based modeling explained approximately 50%-90% of the GxE variations. C_LI

plant biology↗

bioRxiv2022

Global soil metagenomics reveals ubiquitous yet previously-hidden predominance of Deltaproteobacteria in nitrogen-fixing microbiome

Biological nitrogen fixation is a fundamental process sustaining all life on earth. In the soil, Alphaproteobacteria, Betaproteobacteria, and Cyanobacteria are traditionally considered the major groups of nitrogen fixation population. This conventional knowledge has been accumulated by numerous PCR amplicon surveys for nitrogenase genes. However, this prevalent view appears to be inconsistent with results of recent PCR-free meta-omics investigations. Here, we show the global distribution and diversity of terrestrial diazotrophic microbiome, updated by fully leveraging the planetary collections of soil metagenomes along with recently expanded culture collections. After extensive analysis of 1,445 soil metagenomic samples, we proved that the previously-undervalued Anaeromyxobacteraceae and Geobacteraceae within Deltaproteobacteria are ubiquitous and predominant groups of diazotrophic microbiome in the soils, spanning a broad spectrum of environments, with different geographic origins and land usage types, including aerobic (croplands, grasslands) and anaerobic ones (paddy soils, sediments). Our results delineate a revised scheme of soil nitrogen fixation, which is inclusive of both conventional diazotrophs and the so far undervalued Deltaproteobacteria.

microbiology↗

bioRxiv2022

KIF24 controls the clustering of supernumerary centrosomes in pancreatic ductal adenocarcinoma cells

Clustering of supernumerary centrosomes, potentially leading to cell survival and chromosomal instability, is frequently observed in cancers. However, the molecular mechanisms by which centrosome clustering is controlled in cancer cells remain largely unknown. A centrosomal kinesin, KIF24, was previously shown to restrain the assembly of primary cilia in mammalian cells. Here, we revealed that KIF24 depletion suppresses multipolar spindle formation by clustering centrosomes in pancreatic ductal adenocarcinoma (PDAC) cells harboring supernumerary centrosomes. KIF24 depletion also induced hyperproliferation and improved the mitotic progression in PDAC cells. On the other hand, disruption of primary cilia failed to affect the proliferation and spindle formation in KIF24-depleted cells. These results represent a novel role of KIF24 in suppressing centrosome clustering independent of primary ciliation in centrosome-amplified PDAC cells.

cell biology↗

bioRxiv2022

Atypical small GTPase RABL3 interacts with RAB11 to regulate early ciliogenesis in human cells

Primary cilia are near-ubiquitously assembled on cells in the human body and are broadly associated with genetic diseases and cancers. In the early stage of ciliogenesis, the ciliary vesicle (CV) is formed on the mother centriole, which nucleates the primary cilium. However, the regulatory mechanisms underlying CV formation have not yet been fully elucidated. Here, we found that the atypical small GTPase RAB-Like 3 (RABL3) is necessary to assemble primary cilia in human cells. RABL3 directly interacts with RAB11, which is involved in CV formation. RABL3 localizes around the centrosome during early ciliogenesis, reminiscent of RAB11 dynamics. Furthermore, RABL3 positively controls the CV formation like RAB11. These findings suggest that RABL3 plays an important role, in cooperation with RAB11, in CV formation during early ciliogenesis.

cell biology↗

bioRxiv2019

Efficacy and safety of a monodisperse solid-in-oil-in-water emulsion in transcatheter arterial chemoembolization in a rabbit VX2 tumor model

Transcatheter arterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma; however, it does not always result in tumor control. Nevertheless, treatment outcome can be improved with monodisperse emulsions of anticancer agents. In this study, the efficacy and safety of a monodisperse miriplatin-Lipiodol emulsion were evaluated in Japanese white rabbits. VX2 tumor was implanted into the left liver lobe of each rabbit. The animals were divided into control and experimental groups (of five animals each) and respectively administered a conventional miriplatin suspension or the emulsion via the left hepatic artery. Computed tomography (CT) was performed before, immediately after, and two days following TACE. All rabbits were sacrificed two days after the procedure. Each tumor was removed and cut in half for assessment of iodine concentration in one half by mass spectroscopy and evaluation of Lipiodol accumulation and adverse events in the other half. Mean Hounsfield unit (HU) values were measured using plain CT images taken before and after TACE. Iodine concentration was higher in the experimental group [1100 (750-1500) ppm] than in the control group [840 (660-1800) ppm]. Additionally, the HU value for the experimental group was higher than that for the control group immediately after [199.6 (134.0- 301.7) vs. 165.3 (131.4-280.5)] and two days after [114.2 (56.1-229.8) vs. 58.3 (42.9-132.5)] TACE. Cholecystitis was observed in one rabbit in the control group. Ischemic bile duct injury was not observed in any group. The results show that Lipiodol accumulation and retention in VX2 tumor may be improved by using a monodisperse emulsion. Moreover, no significant adverse events are associated with the use of the emulsion.

pharmacology and toxicology↗